Association of antigen-specific T-cell responses with antigen expression and immunoparalysis in multiple myeloma

• Verfasst von: Fichtner, Sabrina [VerfasserIn]
• Verfasst von: Hose, Dirk [VerfasserIn]
• Verfasst von: Engelhardt, Melanie [VerfasserIn]
• Verfasst von: Meißner, Tobias [VerfasserIn]
• Verfasst von: Neuber, Brigitte [VerfasserIn]
• Verfasst von: Krasniqi, Fatime [VerfasserIn]
• Verfasst von: Raab, Marc-Steffen [VerfasserIn]
• Verfasst von: Schönland, Stefan [VerfasserIn]
• Verfasst von: Ho, Anthony Dick [VerfasserIn]
• Verfasst von: Goldschmidt, Hartmut [VerfasserIn]
• Verfasst von: Hundemer, Michael [VerfasserIn]
• Titel: Association of antigen-specific T-cell responses with antigen expression and immunoparalysis in multiple myeloma
• Verf.angabe: Sabrina Fichtner, Dirk Hose, Melanie Engelhardt, Tobias Meißner, Brigitte Neuber, Fatime Krasniqi, Marc Raab, Stefan Schönland, Anthony D. Ho, Hartmut Goldschmidt, and Michael Hundemer
• E-Jahr: 2015
• Jahr: January 21, 2015
• Umfang: 10 S.
• Fussnoten: Gesehen am 08.01.2021
• Titel Quelle: Enthalten in: Clinical cancer research
• Ort Quelle: Philadelphia, Pa. [u.a.] : AACR, 1995
• Jahr Quelle: 2015
• Band/Heft Quelle: 21(2015), 7, Seite 1712-1721
• ISSN Quelle: 1557-3265
• DOI: doi:10.1158/1078-0432.CCR-14-1618
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1744266646

Abstract

Purpose: Cancer testis antigens (CTA) are immunotherapeutical targets aberrantly expressed on multiple myeloma cells, especially at later stages, when a concomitant immunoparesis hampers vaccination approaches. - Experimental Design: We assessed the expression of the multiple myeloma antigen HM1.24 (reported present in all malignant plasma cells) and the CTAs MAGE-A2/A3 and NY-ESO-1 (aberrantly expressed in a subset of patients with myeloma), in CD138-purified myeloma cells by qRT-PCR (n = 149). In a next step, we analyzed the antigen-specific T-cell responses against these antigens by IFNγ EliSpot assay (n = 145) and granzymeB ELISA (n = 62) in relation to stage (tumor load) and expression of the respective antigen. - Results: HM1.24 is expressed in all plasma-cell samples, whereas CTAs are significantly more frequent in later stages. HM1.24-specific T-cell responses, representing the immunologic status, significantly decreased from healthy donors to advanced disease. For the CTAs, the probability of T-cell responses increased in early and advanced stages compared with healthy donors, paralleling increased probability of expression. In advanced stages, T-cell responses decreased because of immunoparesis. - Conclusion: In conclusion, specific T-cell responses in myeloma are triggered by antigen expression but suppressed by tumor load. Future CTA-based immunotherapeutical approaches might target early plasma-cell diseases to establish prophylactically a specific T-cell response against late-stage antigens in immunocompetent patients. Clin Cancer Res; 21(7); 1712-21. ©2015 AACR.